Even though the chronic non-medical use of cocaine has currently reached epidemic proportions in this country, there is as yet no clear-cut consensus among health care professionals regarding optimal treatment strategies for cocaine abuse. The introduction of pharmacological interventions to increase the probability of successful cocaine abstinence has only recently been investigated since chronic cocaine use has not historically been assumed to produce prolonged physiological withdrawal symptoms upon discontinuation. However, since some individuals can remain casual recreational users of the drug, there may be factors in addition to cocaine's reinforcing properties that determine why other individuals progress to compulsive drug use. In fact, a subpopulation of chronic cocaine users may actually be self-medicating to regulate painful feelings and psychiatric symptoms via their drug use. A better understanding of potential environmental events that can alter drug-intake will increase knowledge of the etiology of drug addiction and may result in the more effective and efficient treatment of compulsive cocaine use and withdrawal. Changes in the amount or severity of environmental stress or anxiety may be one factor which predisposes some individuals to engage in compulsive drug use since both clinical and preclinical data have implicated an involvement of benzodiazepines in the behavioral and neurobiological effects of cocaine during both acute exposure and withdrawal from the chronic use of the drug. The experiments described in this proposal will therefore be used to systematically investigate the effects of controllable and uncontrollable electric footshock stress on the acquisition and maintenance of intravenous cocaine self-administration in rats. In addition, this behavioral model will be used as a baseline to evaluate whether various pharmacological interventions specifically alter drug-intake and/or the behavioral effects of withdrawal from cocaine or whether these drugs result in nonspecific effects on the ability of the animals to respond. The results of these investigations will increase knowledge of behavioral variables that potentially contribute to cocaine self-administration in rats and may therefore result in the development of novel pharmacotherapies in the treatment of cocaine withdrawal and abstinence in humans.